The present invention relates to methods of using cartilage producing cells, such as chondrocytes, for repairing cosmetic defects such as skin contour irregularities. The present invention further relates to implantable medical devices coated with chondrocytes and, more particularly to coating of implants (natural and artificial) with chondrocytes and or and/or their progenitors as a means of reducing unfavorable host response to the implant.
Cosmetic Repair
Plastic surgeons, dermatologists and their patients continually search for new and approved methods for treating damaged or aging skin. Historically, the treatment of facial wrinkles was primarily accomplished with the use of chemical peels or dermabrasion. The use of chemical peels has fallen out of favor, because it is difficult to accurately control and predict the depth of tissue injury after such peels are applied. Deeper chemical peels in particular have an increased risk of hypopigmentation and scarring.
Soft tissue fillers, such as collagen, have also been used for treatment of skin imperfections. These fillers are typically injected subcutaneously in a manner which enables filling and thus smoothing out skin contour irregularities such as wrinkles and scars.
Use of collagen as a dermal filler has several inherent disadvantages. These disadvantages typically include dissolution within 3 months, localized hypersensitivity in 1-6% of subjects, hypopigmentation, induration and multiple nodules as a result of foreign body granulomas (Boss et al. (2000) Clinics in Plastic Surgery 27(4): 613-626).
Synthetic dermal fillers offer an alternative to collagen. However, commercially available fillers such as Artecoll™, silicone and hyaluronen™ have not been approved for use in the United States. Further, some subcutaneous fillers, such as AlloDerm™ and SoftForm™ require surgical insertion, and might result in infection, reabsorption, malposition and rejection (Boss et al. (2000) Clinics in Plastic Surgery 27(4): 613-626).
Medical Implants
Non-self implants are used in many fields of medicine, such as: plastic surgery, orthopedics, maxillo-facial surgery, etc. The main disadvantage of prior art implants is the physiologic response they provoke following implantation. This response, which is typically induced locally around such implants is the body's attempt to reject the implant, or to isolate it from the body by creating a capsule around it. While a capsule may isolate the implant from a systemic immune response, it can also contract and cause distortion and pain of the organ. For example, a breast prosthesis induces capsule formation around it. In a study by Melmed (Plast Reconstr Surgery (1998) 101(5): 1364-73) 66% of the implanted women had severe capsular-contracture (III or IV Baker Degree).
Several approaches for reducing the physiological response to an implant have been suggested in the prior art. For example, Nishibe et al. (J Cardiovasc Surg (Torino) 2001 42(5):667-73) describe bonding of fibronectin to high porosity expanded polytetrafluoroethylene grafts as a means of improving host acceptance of implants. Rinsch et al. (Transplantation 2000 Feb. 15;71(3):345-51) teach transient immunosuppression as a means of increasing host tolerance for encapsulated xenogenic cells implanted into a subject. Neither of these methods employs cells. As such, the effect must be transient.
There is thus a widely recognized need for, and it would be highly advantageous to have, methods of using chondrocytes to effect cosmetic repair and chondrocyte coated implants devoid of the above limitation.